Urine metabolomic analyses reveal metabolite disruptions in steroid hormone biosynthesis in monkeypox

Monkeypox virus (MPXV) poses a global health threat. Viral infection can alter host metabolic homeostasis, while its changes may influence disease severity and progression. The relationship between MPXV and metabolites has not been reported. we employed metabolomics to characterize the mpox specific metabolic features by comparing changes in urinary metabolites from patients with MPXV infection, HIV infection, and HIV-MPXV co-infection. The metabolic changes caused by MPXV were mainly concentrated in amino acid and hormone metabolism. Further analysis showed that 5'-dihydroadenosine and uric acid can serve as potential molecular markers for MPXV and HIV-MPXV co-infected patients, respectively. Confirmed by targeted metabolomics and ELISA methods, MPXV infection caused severe disorders in the metabolic pathways of steroid hormones such as testosterone and progesterone in humans. Our findings identify dysregulated metabolism as an underpinning of MPXV pathogenicity, and increasing the anti-inflammatory capacity of patients may play a role to some extent against mpox.